Remote regulation of rs80245547 and rs72673891 mediated by transcription factors C-Jun and CREB1 affect GSTCD expression

• Published in: iScience 2023-08, Vol.26 (8), p.107383-107383, Article 107383
• Main Authors: Li, Jin-Xiu, Huang, Xue-Zhen, Fu, Wei-ping, Zhang, Xiao-hua, Mauki, David H., Zhang, Jing, Sun, Chang, Dai, Lu-Ming, Zhong, Li, Yu, Li, Zhang, Ya-ping
• Format: Article
• Language: English
• Subjects: Biological sciences; Genomics; Molecular biology; Molecular Genetics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107383

Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is influenced by genetic factors. The genetic signal rs10516526 in the glutathione S-transferase C-terminal domain containing (GSTCD) gene is a highly significant and reproducible signal associated with lung function and COPD on chromosome 4q24. In this study, comprehensive bioinformatics analyses and experimental verifications were detailly implemented to explore the regulation mechanism of rs10516526 and GSTCD in COPD. The results suggested that low expression of GSTCD was associated with COPD (p = 0.010). And C-Jun and CREB1 transcription factors were found to be essential for the regulation of GSTCD by rs80245547 and rs72673891. Moreover, rs80245547T and rs72673891G had a stronger binding ability to these transcription factors, which may promote the allele-specific long-range enhancer-promoter interactions on GSTCD, thus making COPD less susceptible. Our study provides a new insight into the relationship between rs10516526, GSTCD, and COPD. [Display omitted] •The low expression of GSTCD mRNA is associated with COPD•Rs80245547 and rs72673891 regulate GSTCD through remote enhancer-promoter interactions•C-Jun and CREB1 are necessary for rs80245547 and rs72673891 to regulate the GSTCD gene•Rs80245547T and rs72673891G had a stronger binding ability to C-Jun and CREB1 Biological sciences; Molecular biology; Molecular Genetics; Genomics.